RECRUITING

Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma

Conditions

B-cell Non-Hodgkin Lymphoma (B-NHL)Relapsed/Refractory B-NHL Universal Chimeric Antigen Receptor T-Cell (UCAR-T) Therapy Allogeneic Transcription Activator-Like Effector Nuclease (TALEN®)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

First-in-human, open-label, dose-finding and dose-expansion study of UCART20x22 administered intravenously in subjects with relapsed or refractory B-Cell Non-Hodgkin Lymphoma (B-NHL). The purpose of this study is to evaluate the safety and clinical activity of UCART20x22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).

Official Title

Open-label Dose-finding and Dose-expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of UCART20x22 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (B-NHL)

Quick Facts

Study Start:2022-11-01

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05607420

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22 * Subjects with NHL subtypes defined by WHO: * -Dose-Finding Part: R/R mature B-NHL (except chronic lymphocytic leukemia/small lymphocytic leukemia \[CLL/SLL\], Richter's transformation from prior CLL/SLL, Burkitt's lymphoma, and Waldenstrom's macroglobulinemia) * -Dose-Expansion Part: R/R LBCL, defined as: i. DLBCL; ii. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; iii. Transformed FL or transformed marginal zone lymphoma (MZL); iv. Follicular lymphoma Grade 3B * R/R disease after at least 2 lines of prior treatment, which must have included: * -An Anti-CD20 MoAb and an anthracycline for DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma (PMBCL), or transformed FL or MZL * -An alkylating agent in combination with an anti-CD20 MoAb for FL * -An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton's tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL) * -Autologous anti-CD19 CAR T-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-CD19 CAR T-cell therapy (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, CD19 negative disease, etc.) * Autologous hematopoietic stem cells must be available prior to the start of the LD regimen if the subject is considered high-risk for prolonged hematologic toxicity	* Prior use of an investigational product (except for cell or gene therapies and MoAbs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of LD regimen * Previous approved therapy including chemotherapy, biologic (except MoAbs), or targeted therapy for R/R B-NHL with 5 half-lives or within 14 days, whichever is shorter, prior to start of the LD regimen * Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD * Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen * Prior cell or gene therapy (approved or investigational) within 6 weeks of the start of LD * Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22 * Autologous HSCT infusion within 6 weeks of the start of LD * Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD * Active acute or chronic graft versus host disease (GvHD). Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD * Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen) * Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL * Presence of an active and clinically relevant CNS disorder * Daily treatment with \>20 mg prednisone or equivalent * Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens * History of hypersensitivity to alemtuzumab * History of neutralizing anti-drug antibody against alemtuzumab * Any known uncontrolled cardiovascular disease within 3 months of enrollment * Subjects requiring immunosuppressive treatment * Major surgery within 28 days prior to start of LD * Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix)

Inclusion Criteria

Exclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22
* Subjects with NHL subtypes defined by WHO:
* -Dose-Finding Part: R/R mature B-NHL (except chronic lymphocytic leukemia/small lymphocytic leukemia \[CLL/SLL\], Richter's transformation from prior CLL/SLL, Burkitt's lymphoma, and Waldenstrom's macroglobulinemia)
* -Dose-Expansion Part: R/R LBCL, defined as: i. DLBCL; ii. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; iii. Transformed FL or transformed marginal zone lymphoma (MZL); iv. Follicular lymphoma Grade 3B
* R/R disease after at least 2 lines of prior treatment, which must have included:
* -An Anti-CD20 MoAb and an anthracycline for DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma (PMBCL), or transformed FL or MZL
* -An alkylating agent in combination with an anti-CD20 MoAb for FL
* -An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton's tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL)
* -Autologous anti-CD19 CAR T-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-CD19 CAR T-cell therapy (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, CD19 negative disease, etc.)
* Autologous hematopoietic stem cells must be available prior to the start of the LD regimen if the subject is considered high-risk for prolonged hematologic toxicity

* Prior use of an investigational product (except for cell or gene therapies and MoAbs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of LD regimen
* Previous approved therapy including chemotherapy, biologic (except MoAbs), or targeted therapy for R/R B-NHL with 5 half-lives or within 14 days, whichever is shorter, prior to start of the LD regimen
* Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD
* Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen
* Prior cell or gene therapy (approved or investigational) within 6 weeks of the start of LD
* Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22
* Autologous HSCT infusion within 6 weeks of the start of LD
* Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD
* Active acute or chronic graft versus host disease (GvHD). Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
* Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen)
* Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL
* Presence of an active and clinically relevant CNS disorder
* Daily treatment with \>20 mg prednisone or equivalent
* Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
* History of hypersensitivity to alemtuzumab
* History of neutralizing anti-drug antibody against alemtuzumab
* Any known uncontrolled cardiovascular disease within 3 months of enrollment
* Subjects requiring immunosuppressive treatment
* Major surgery within 28 days prior to start of LD
* Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix)

Contacts and Locations

Study Contact

Cellectis Central Contact

CONTACT

+1 917 580-1088

clinicaltrials@cellectis.com

Principal Investigator

Jeremy Abramson, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

University of Chicago

Chicago, Illinois, 60637

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

United States

Sarah Cannon - St. David South Austin Medical Center

Austin, Texas, 78704

United States

Collaborators and Investigators

Sponsor: Cellectis S.A.

Jeremy Abramson, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-01

Study Completion Date2027-11

Study Record Updates

Study Start Date2022-11-01

Study Completion Date2027-11

Terms related to this study

Keywords Provided by Researchers

B-cell Non-Hodgkin Lymphoma (B-NHL)
Relapsed/Refractory B-NHL
Universal Chimeric Antigen Receptor T-Cell (UCAR-T) Therapy
Allogeneic
Transcription Activator-Like Effector Nuclease (TALEN®)

Additional Relevant MeSH Terms

B-cell Non-Hodgkin Lymphoma (B-NHL)